Herbert Bonkovsky

Herbert L. Bonkovsky, MDProfessor of MedicineSenior Advisor for Research, Carolinas HealthCare SystemDirector of Liver, Digestive, and Metabolic Disorders LaboratoryDepartment of Internal MedicineProfessor, University of ConnecticutProfessor, University of North Carolina at CharlotteProfessor, University of North Carolina at Chapel Hill

Clinical and Translational Research in Liver, Digestive, and Metabolic Diseases

Throughout a medical career now spanning more than 40 years, Dr. Bonkovsky has been committed to Clinical and Translational Research. His research career began in medical school when he performed studies on interactions of iron with mitochondria in the laboratories of L.T. Webster, Jr. and J.W. Harris at Case Western Reserve University School of Medicine. This began a continuing interest in the study of iron metabolism and disorders of iron metabolism, especially various forms of hemochromatosis. During this time, Dr. Bonkovsky also worked closely with G. Gabuzda and L. Shear. This work led to a landmark paper that described clearly the occurrence of renal tubular acidosis in a subset in patients with hepatic cirrhosis and its importance as a risk factor for development of hepatic encephalopathy [NEJM 1969; 280: 1-7].

Dr. Bonkovsky spent two years as a clinical associate in the Metabolism Branch in the National Cancer Institute, where his mentors were N.I. Berlin and D.P. Tschudy. During this time, he carried out groundbreaking studies in the laboratory and in the general clinical research center on the nature of the enzymatic defects that underlie the porphyrias. He was among the first to show that hepatic porphyrin and heme synthesis is under the negative feedback regulatory control of heme itself, acting chiefly to down-regulate delta-aminolevulinic acid (ALA) synthase-1 the rate controlling enzyme for heme synthesis. This led Dr. Bonkovsky to develop parenterally-administered heme as therapy of acute attacks of porphyria, which is still today the treatment of choice for these life-threatening attacks.

In other work on the porphyrias, Dr. Bonkovsky identified deficiency of ferrochelatase, the final enzyme in the heme synthetic pathway as the fundamental metabolic defect in erythropoietic protoporphyria. Studies on the regulation of hepatic heme metabolism, especially the mechanisms and factors that regulate ALA synthase and heme oxygenase have been the subject of a large number of studies, both in the basic research laboratory and the clinical research center during the past 25 years. Dr. Bonkovsky has been fortunate to have had major RO1 grant funding from NIH (NIDDK) continually for the past quarter century to help support this research. Dr. Bonkovsky serves as one of the Principal Investigators of the U.S. Porphyria Consortium, one of the Rare Diseases Consortia, supported by the NIH and Office of Rare Diseases Research. CHS is one of six clinical sites across the country that serve as Clinical Centers of Excellence in the Porphyrias.

Other areas of special interest and accomplishment have more recently included a number of clinical trials and studies in chronic viral hepatitis, especially chronic hepatitis C. Dr. Bonkovsky continues to serve as one of the principal investigators of the NIH-sponsored HALT-C Trial, which has been designed to try and improve the treatment and outcome for patients with difficult to cure chronic hepatitis C. He has performed a number of investigator-initiated and industry-sponsored trials of possible new therapies for chronic hepatitis C, including phase 1 to phase 4 studies. Because the conquest of chronic hepatitis C continues to be elusive, Dr. Bonkovsky continues to be actively involved in such studies now carried out at the Center for Clinical and Translational Research at Carolinas Medical Center.

Another major cause of liver disease is liver injury due to drugs and other chemicals. Dr. Bonkovsky has performed both basic and clinical studies on alcoholic liver disease and its management and on drug-induced liver injury (DILI). He is one of the principal investigators of the NIH–supported national Drug Induced Liver Injury Network (DILIN). This ongoing active network has developed a registry of patients with clinically important DILI and repositories of serum, DNA, urine and other samples from such patients. Other ongoing activities of the network include several important ancillary studies examining the genetic underpinnings of toxicity caused by drugs and chemicals, genome wide association studies looking for new genetic variations that increase the risk of development of DILI, the characterization of infiltrating lymphocytes in liver biopsies of patients with DILI and the development of improved laboratory methods for lymphocyte stimulation tests as an aide to the diagnosis of DILI and the assignation of causative agents in DILI.

The overarching vision of Dr. Bonkovsky for research at Carolinas HealthCare System is to develop core facilities and infrastructure needed for investigators throughout the system to be successful and productive in performing both bench and clinical and translational research of all kinds that is at the cutting edge with the ultimate goals always to relieve human suffering and improve the art and science of contemporary medicine.